Two human mast cell types were identified by immunohistochemical techniques in skin, lung, and small intestine. One type contains the neutral proteases, tryptase and chymotryptic proteinase, and is termed the TC mast cell. The second type contains only tryptase and is termed the T mast cell. Both types are fixed better by Carnoy's fluid than by formalin. The percentage of mast cells accounted for by the T type was 12 in skin; 98 in mucosa and 13 in submucosa of small intestine; and 77 in bronchial/bronchiolar subepithelium, about 97 in bronchial/bronchiolar epithelium, and 93 in alveoli of lung. Dispersed lung cells contained 90% T mast cells. The mean area of TC mast cells (76 micron2) was slightly larger than that of T mast cells (66 micron2); however, there was such extensive overlap that individual mast cells belonging to different types could not be distinguished on the basis of size. The recognition of human mast cell types with distinct protease compositions suggests a higher level of complexity of human mast cell-mediated reactions than heretofore appreciated.